Novel 2,5-disubstituted thiazole carboxaldehyde and derivatives of the same

ABSTRACT

The present invention relates to novel 2,5-disubstituted mononitro thiazoles and to methods for their preparation. These compounds are used for controlling or inhibiting the growth of microorganisms, fungi and nematodes.

United States Patent Berkelhammer et al. July 4, 1972 591 NOVEL2,5-DISUBSTITUTED 58 Field of Search ..260/240 0 THIAZOLE CARBOXALDEHYDEAND DERIVATIVES OF THE SAME [561 References CM [72] Inventors: GeraldBerkelhammer, Princeton; Goro UNITED STATES PATENTS Asato, Titusville,both of N.J.; Edward 4 4 l l n 260 302 Leslie Moon, St. petersburg, Fla.3,505,3 6 I970 Berkelhammer et a [73] Assignee: American CyauamidCompany, Stamford, OTHER PUBLICATIONS Coml- German Printed Application(Auslegeschrift) No. 1,159,450, [22] Filed: Jan. 19, 1970 published Dec.19, 1963, 3 pages [21] AppLNo; 4,049 Primary Examiner-John D. RandolphAttorney-Robert P. Raymond Related U.S. Application Data [63]Continuation-in-part of Ser. No. 598,209, Dec. 1, [571 ABSTRACT 19663,505,346 which is a continuation'in' The present invention relates tonovel 2,5-disubstituted P of 515,442 21, 1965, abandoned mononitrothiazoles and to methods for their preparation. These compounds are usedfor controlling or inhibiting the [52] U.S. Cl. ..260/240 G, 7 H902,growth f microorganisms f i and nematodes [51] Int. Cl. ..C07d 91/32 4Claims, N0 Drawings NOVEL 2,5-DISUBS'ITI'UTED THIAZOLE CARBOXALDEHYDEAND DERIVATIVES OF THE SAME This application is a continuation-in-partof our copending application, Ser. No. 598,209, filed on Dec. 1, 1966,now US. Pat. No. 3,505,346, issued on Apr. 7, 1970, which is in turn acontinuation-in-part of our copending application, Ser. No, 515,442,filed on Dec. 21, 1965, now abandoned.

The present invention relates to a novel class of 2,5-disub stitutedthiazoles and to methods for their preparation. More specifically, theinvention relates to substituted thiazole carboxaldehydes andderivatives thereof, to methods for preparing the same and has as aprincipal object thereof, the utilization for controlling or inhibitingthe growth of microorganisms, fungi and nematodes.

The novel substituted thiazolecarboxaldehydes and derivatives thereof ofthis invention can be represented by the graphic structure:

No,, Cl-l0, -CH NR or Cl-l CHR X or Y but not both is NO2;

provided that R stands for the substituent:

s NH( )NHe,NHi NHe -H, a saturated five-membered-mononitrogenheterocycle, a saturated five-membered-dinitrogen heterocycle or asaturated five-membered-motQgnitrogen-monooxygen heterocycle, each ofwhich heterocycle contains at least one but not more than two carbonylgroups attached to the heterocyclic moiety; R represents a six-memberednitrogen heterocycle, such as pyridyl or quinolyl; and R" stands for theradical: H or COCH as well as the acid addition or quaternary am moniumsalt thereof.

Illustrative compounds which fall within the purview of the inventionare: 2-[2-(5-nitro-2-thiazolyl)vinyl]pyridine, 2-nitro-S-thiazolecarboxaldehyde, -nitro-2-thiazolecarboxaldehyde, 3-{[ (5nitro-2-thiazolyl)methylidene]amino{-2-oxazolidinone,2-nitro-5-thiazo1ecarboxaldehyde, 3-{[(2-nitro-5-thiazolyl)methylidene]amino}-2-oxazolidinone, 2-nitro-5-thia-zolecarboxaldehyde thiosemicarbazone, 2-amino-5-(2-nitro-5-thiazolyl)- l ,3 ,4-thiadiazole, Z-nitro-S-thiazolyl)methylidene]amino}hydantoin, l-{[(2-nitro-5-thiazolyl)methylideneJ-amino -2-imidazolidinone, 2-nitro-5-thiazolec'arboxaldehyde oxime, 4-[2-(5-nitro-2-thiazolyl)vinyljpyridine,2[2-(5-nitro-2-thiazolyl)vinyllquinoline,lr'nethyl-2-[2-(5-nitro-2-thiazolyl)vinyllpyridinium iodide, 5-nitro-2-thiazolecarboxaldehyde thiosemicarbazone, 2-amino-5-(5-nitro-2-thiazolyl)-l,3,4-thiadiazole, l-'{[(5-nitro-2-thiazolyl)methylidene]amino}hydantoin, l-{ 5-nitro-2-thiazolyl)methylidene]amino}-2-imidazolidinone, 5-nitro-2-thiazolecarboxaldehyde oxime, 5-nitro-2-thiazolecarboxaldehydesemicarbazone, and 2-acetamido-5-(5-nitro-2- thiazolyD-l,3,4-thiadiazole.

In general, the above-illustrated compounds can be readily prepared fromwell-known intermediates. For instance, to repare5-nitro-2-thiazolecarboxaldehyde, 2-amino-5-nitrothiazole and alkalimetal nitrite, such as sodium nitrite, are admixed in equimolarproportions in the presence of concentrated hydrochloric acid. Themixture is then inin'ally cooled, usually to below about 50 C. andtreated with about 1.5 moles of vinyl pyridine. There is then obtained2-[2-(5-nitro 2thiazolyl)vinyl]pyridine. When the latter is treated withozone in the presence of a lower alkyl ester solvent, such asethylacetate, 5-nitro-2-thiazolecarboxaldehyde is recovered in goodyield.

The preparation of S-nitro-Z-thiazolecarboxaldehyde derivativescontemplated herein involves the reaction of thenitrothiazolecarboxaldehyde with an amine or methyl heterocyclicreactant, such as RNl-l, or R'CH where R and R are the same ashereinabove defined. In brief, when utilizing RCl-l as the reactant, thenitrothiazolecarboxaldehyde is dissolved in an inert solvent therefor,such as alcohol, dioxane, or dimethylsulfoxide. To the solution is thenadded with stirring, catalytic quantities of zinc chloride, piperidine,or a strong mineral acid, together with the methyl heterocyclicreactant, such as 2- or 4-picoline or quinaldine. Where RNl-l is thereactant, the latter amine reactant, such as hydroxylamine,semicarbazide, 3-amino-2-imidazolidinone, 3-amino-2-oxazolidinone, orthiosemicarbazide, is permitted to react with the nitrothiazole in aninert solvent, usually alcohol or aqueous alcohol. Advantageously, thereaction may be catalyzed by a small amount of mineral acid, such ashydrochloric acid. Usually, equimolar quantifies of reactants but widelyvarying temperatures from about 0 to C. can be employed for purposes ofconducting the process of the invention.

The invention will be further exemplified by the following illustrativeexamples which are not to be taken as being limitative.

EXAMPLE 1 2-[ 2-( 5-Nitro-2-thiazolyl)vinyl]pyridine Preparation In asuitable reaction vessel one mole grams) of 2- amino-5-nitrothiazole isslurried with 450 milliliters of concentrated hydrochloric acid and 100milliliters of water and cooled to 70 C.; in one-half hour, 69 grams 1mole) of sodium nitrite in 100 milliliters of water is added to give apale green mixture. Subsequently, after 10 minutes of stirring, grams(1.52 moles) of vinylpyridine in 600 milliliters acetone is addedrapidly, keeping the temperature below 3 0 C. Then 28 grams of cupricchloride dihydrate is added and the mixture stirred 10 minutes beforeallowing it to rise to room temperature. At l0 C. the greenish mixtureturns reddish and the vigorous evolution of nitrogen is noted. Themixture is stirred at room temperature until nitrogen evolution ceases.The latter is then added to half a liter of water. The mixture isneutralized with sodium bicarbonate, treated with methylene chloride(five pints), filtered and the organic phase separated. The aqueousphase or layer is further extracted with methylene chloride and thecombined and dried with magnesium sulfate. After filtering. the volatileliquids are removed from the filtrate in vacuo to give a viscous mixturewhich contains solid material.

The above prepared mixture is washed with methanol to give 25.3 grams ofsolid product, having a melting point between 178 C.-182 C. Evaporationof the mother liquors afiords an additional six grams of product whichbegins to melt at 162 C. Purification of products by treatment of achloroform solution with activated carbon affords 25.43 grams or 10.5percent of yellow product. The pure product melts at between l81.5 C.and 183C.

EXAMPLE 2 Preparation of 5-Nitro-2-thiazolecarboxaldehyde Twelve grams(51.5 m moles) of 2-[2-(5-nitro-2- thiazolyl)vinyl]pyridine in 450milliliters of ethylacetate is slurried at between --30 C. and 20 C.Ozone is introduced for one and one-half hours or until the yellow colordisappears. Stirring is continued for an additional 10 minutes beforethe mixture is purged of ozone with nitrogen. The mixture is thentreated with 9 grams of sodium iodide in 10 milliliters of glacialacetic acid and 100 milliliters of water at from -10 C. to 10 C. Theiodine is reduced with 19 grams of sodium thiosulfate in 200 millilitersof water, the organic phase separated, and the aqueous layer extractedwith 100 milliliters of ether.

combined organic phases are Preparation of 3-{ [(-Nitro-2-thiazolyl)methylidene]amino} -2-oxazolidinone 4.16 Grams of5-nitro-2-thiazolecarboxaldehyde in 35 milliliters of ethanol is treatedwith 2.7 grams (26.4 m moles) of 3-amino-2-oxaz lidinone and five dropsof concentrated hydrochloric a 'd to give a yellow solid. The mixture isslurried, refluxed for 5 minutes, cooled, and the yellow productcollected by filtration. The solid is washed with cold 2B ethanol anddried to give 5.52 grams (86.4 percent) of product, whose melting pointis 221 C.-222 C.

EXAMPLE 4 Preparation of 4-[ 2-( 5-Nitro-2-thiazolyl)vinyl]pyridine In15 milliliters of n-propanol with 0.5 milliliters of piperidine areplaced 4.4 grams of 5-nitro-2-thiazolecarboxaldehyde and 1.3 grams of4-picoline. The mixture is heated at reflux for one hour, cooled, andthe solid collected by filtration. The material is recrystallized frommethanol to give a yellow product, melting point 167 C. -1 69 C.

EXAMPLE 5 Preparation of 2-[2-(5-Nitro-2-thiazolyl)vinyl]quino1ine Amixture of 15.8 grams of 5-nitro-2-thiazolecarboxaldehyde and 7.2 gramsof quinaldine in 100 milliliters of npropanol and 2 milliliters ofpiperidine is heated at reflux for three hours. The resulting mixture iscooled in ice for one hour and the solid collected by filtration. Theproduct is recrystallized from hot acetone, a process which affordsyellow crystals melting at 208-209 C.

EXAMPLE 6 Preparation of 1-Methy1-2-[2-( 5-Nitro-2-thiazolyl)vinyl]-pyridinium iodide In a glass pressure bottle fitted with a sealing capis placed 5.0 grams of 2-[2-(5-nitro-2-thiazolyl)vinyl]pyridine and 100grams of methyl iodide. The device is sealed and immersed for eighthours in an oil bath maintained at 100 C. The temperature of the oilbath is then raised to 145 C. for an additional eight hours. The deviceis removed from the bath, cooled, and the contents washed repeatedlywith hot acetone until a yellow color is no longer present in the wash.The acetone insoluble product is dried in vacuo to give 7.3 grams (90percent) of purple crystals melting at 241-242 C.

EXAMPLE 7 5-Nitro-2-thiazolecarboxaldehyde Preparation ofthiosemicarbazone 3.3 Grams of thiosemicarbazide is dissolved inmilliliters of hot aqueous ethanol, and a solution of 5.7 grams ofS-nitro- 2-thiazolecarboxaldehyde in 25 milliliters of ethanol is added.The resulting dark red solution is treated with two drops ofconcentrated aqueous hydrogen chloride, a process which causes theseparation of a red crystalline solid. The mixture is cooled in ice for30 minutes and the product collected by filtration. Recrystallizationfrom a mixture of acetone and ethanol affords 7 grams of red crystallineproduct melting at 253254 C. with decomposition.

EXAMPLE 8 Preparation of thiudiuzole A mixture of 655 milligrams of5-nitro-2-thiazolecarboxaldehyde thiosemicarbazone and 5.5 grams offerric ammonium sulfate dodecahydrate in 10 milliliters of water isstirred and heated at -90 C. for 2 hours. The mixture is cooled andfiltered, a process which aflords an orange solid. Recrystallizationfrom a mixture of dimethylformamide and ethanol gives 350 milligrams ofproduct melting at 249 C. with decomposition.

EXAMPLE 9 Preparation of l {[(5-Nitro-2-thiazoly1)methylidene lamino}-hydantoin To a solution of 4.15 grams of l-aminohydantoin hydrochloridein 50 milliliters of warm 70 percent aqueous ethanol is added a solutionof 4.25 grams of 5-nitro-2- thiazolecarboxaldehyde in 20 milliliters ofethanol and the resulting mixture heated at reflux for 25 minutes. Thereaction is cooled in ice for 30 minutes and the resulting solidcollected by filtration. Recrystallization from aqueous ethanol andtreatment with decolorizing carbon affords 1.5 grams of crystallineproduct melting at 144l45 C.

EXAivIPLE 10 Preparation of l-{[(5-Nitro-2-thiazolyl)methylidenelamino}-2-irnidazolidinone To 10 milliliters of a solution containing 0.365moles per liter of 1-amino-2-imidazolidinone, prepared in situ (throughthe nitrosation of 2-imidazolidinone with sodium nitrite in 2N sulfuricacid followed by reduction with powdered zinc), is added a solution of275 milligrams of 5-nitro-2-thiazolecarboxaldehyde in 15 milliliters ofethanol. The solution is heated for 5 minutes on a steam bath, andethanol or water is added until a homogeneous system is obtained. Thesolution is chilled in ice to afford a yellow crystalline solid.Recrystallization from a mixture of dimethylformamide and ethanolaflords 400 milligrams of product melting at 25625 7 C. withdecomposition.

EXAMPLE 1 1 Preparation of 5-Nitro-2-thiazolecarboxaldehyde oxirne Amixture of 3.6 grams of S-nitro-2-thiazolecarboxaldehyde and 3.6 gramsof hydroxylamine hydrochloride in 17 milliliters of absolute ethylalcohol and 17 milliliters of pyridine is heated at reflux for 2 hours.The solvents are removed under reduced pressure and the residue treatedwith 20 milliliters of water. The solid thus obtained is collected byfiltration and washed with 20 milliliters of cold water. The crudeproduct is recrystallized from 200 milliliters of 50 percent aqueousethanol by adding enough acetone to the hot mixture to solubilize thesolid. Treatment with decolorizing carbon while in solution, filteringthrough celite, and chilling in ice affords 2.0 grams of crystallineproduct melting at 169-1 70 C.

EXAMPLE 12 Preparation of S-Nitro-Z-thiazolecarboxaldehyde semicarbazoneTo a solution containing 3.8 grams of 5-nitro-2-thiazolecarboxaldehydein 30 milliliters of ethanol is added approximately 50 milliliters ofwater, the solution becoming turbid. To this solution is added 2.65grams of semicarbazide hydrochloride and 1.98 grams of anhydrous sodiumacetate. The resulting solution is heated at 95 C. for 5 minutes. Thesolution is allowed to cool slowly, a process which causes theseparation of a solid which is collected after 45 minutes and washedwith water. The product is boiled for 35 minutes with milliliters ofethanol, collected by filtration, and dried to give 4.4 grams of productmelting at 284 C. with decomposition.

EXAMPLE 13 Preparation of 2-Acetamido-5-(5-nitro-2-thiazolyl)-1,3,4-thiadiazole In 20 milliliters of acetic anhydride, 5 grams of 2-amino-5-(5-nitro-2-thiazolyl)-1,3,4-thiadiazole is heated at 100 C. for minutes,the mixture cooled, and a solid product in good yield is collected.

EXAMPLE 14 Preparation of 2-Nitro-5-thiazolecarboxaldehyde A solutioncontaining 10.0 grams of Z-antino-S-thiazolecarboxaldehyde in percentfluoboric acid is maintained at 40- 60" C. in a heated addition funnelwhile being added dropwise over 45 minutes to a suspension of 5.0 gramscopper metal powder in 100 milliliters of 23 percent aqueous sodiumnitrite solution at C. During the addition, and for a short timethereafter, the reaction mixture evolves gases. The mixture is allowedto stir for 2 hours, filtered to remove some red solid and residualcopper, and the filtrate extracted three times with 200 milliliters ofbenzene. The extracts are combined and dried over magnesium sulfate.After filtration to remove the drying agent, the benzene is evaporatedunder vacuum to give 6.0 grams of product as a yellow oil which slowlycrystallizes to a yellow solid melting at 78-8 1 C.

EXAMPLE 15 EXAMPLE 16 Preparation of 2-Nitro-5-thiazolecarboxaldehydethiosemicarbazone The procedure of Example 7 is followed in everyrespect except that 4.1 grams of 2-nitro-5-thiazolecarboxaldehyde and2.75 grams of thiosemicarbazide are reacted to obtain 3.4 grams of2-nitro-5-thiazolecarboxaldehyde which melts above EXAMPLE 17Preparation of 2-Amino-5-(2-nitro-5-thiazolyl)-1,3,4- thiadiazole Amixture of 4.6 grams of 2nitro-S-thiazolecarboxaldehydethiosemicarbazone, 40 milliliters of dimethylformamide, and 40milliliters of 25 percent aqueous ferric chloride solution is stirredand heated at 100 C. for 2 hours. Stirring is continued at 25 C. for 17hours. The mixture is treated with 100 milliliters of water, and a brownsolid is obtained. This material is placed in a Soxhlet extractor andextracted with acetone until color is no longer removed from the solid.The acetone is treated with decolorizing carbon and evaporated to give4.4 grams of orange product melting above 300 C.

EXAMPLE 18 Preparation of l-{ [(2-Nitro-5-thiazolyl)methylidene1amino}-hydantoin The procedure of Example 9 is followed except that 4.75 gramsof 2-nitro-S-thiazolecarboxaldehyde and 5.0 grams of l-amino-hydantoinare used. The crystalline product melts at 239-240 C. and weighs 4.4grams.

EXAMPLE 19 Preparation of l-{[(2-Nitro-5-thiazolyl)methylidene]amino}-2-imidazolidinone The procedure of Example 10 is followed except that3.0 grams of 2-nitro-S-thiazolecarboxaldehyde and 110 milliliters ofl-amino-2-imidazolidinone solution are used. The red crystalline productweighs 4.4 grams and melts at 252-254 (I.

EXAMPLE 20 Preparation of Z-Nitro-S-thiazolecarboxaldehyde Oxime Theprocedure of Example 11 is followed except that 2-nitro-S-thiazolecarboxaldehyde is used instead of 5-nitro-2-thiazolecarboxaldehyde. The product obtained after tworecrystallizations from aqueous alcohol is an orange powder melting atl27l 34 C.

Advantageously, as is demonstrated in the examples below, the novelcompounds of the present invention can be incorporated in a variety ofsuitable carriers or diluents. in general, the compounds possessenhanced bacteriotoxic and fungitoxic properties even in extremelydilute concentrations. They also possess good herbicidal and nematocidalproperties. In this respect, less than 0.01 percent and usually from0.001 percent to 0.005 percent of the active compound is employed toobtain percent kill of bacteria or fungi. Further, the compositions ofthe invention can be prepared as a solution by dissolving an activecompound in a water and acetone or alcohol mixture. Alternatively,suitable compositions can be prepared either as a suspension in anon-solvent, or as a dust. Suspensions or dispersions of the thiazolecompound in a carrier, such as water, are useful in the treatment ofplant foliage. If desired, the fungicidal compound can be convenientlyapp lied to foliage by dissolving the compound in a highly volatileliquid carrier, such as dichlorodifluoromethane, maintained underpressure. If desired, the active compound can be dissolved in a lessvolatile solvent, such as benzene, and the solution can be furtheradmixed with a highly volatile liquid carrier under ambient pressures.

For some applications, dusts will be required. These can be prepared bymixing the active compounds with materials, such as clay, fuller'searth, bentonite and pumice. In this manner, seed can be protected fromsoil microorganisms by incorporating the active compound in a solidcarrier, while tumbling seeds with the composition.

The compositions herein may include advantageously any compatiblecommercially available dispersing agent for the active compound of theinvention, particularly when the latter is employed as an aqueoussuspension. Illustrative of such dispersing or surface-active agents arethe fatty acid esters of polyhydric alcohol, the sodium salt ofpolymerized propyl naphthalene, sulfonic acid and the ethylene oxidecondensates of alkylaryl polyether alcohols. It is a good practice toemploy from 1 to 5 parts per 100 parts of the active compound.

EXAMPLE 21 In this example, the antibacterial activity of the compoundsof the instant invention is demonstrated.

Representative compounds are dissolved or suspended in aqueous solutionin sufificient amount to provide a concentration of 100 ppm of testcompound in said solution. Three test organisms, gram negativeAerobacter aerogenes, a common inhabitant of soils and water; grampositive Staphylococcus aureus, found on the skins of humans andanimals; and gram negative Xanthomonas vesicatoria, a pathogen whichincites bacteriosis of tomatoes and peppers are used as the testorganisms.

Nine milliliters of deionized water is introduced into a plurality oftest tubes to be used for evaluation and the tubes are capped andsterilized. For each test compound employed, 1 milliliter of stocksolution is added to each of three test tubes resulting in a testconcentration of 100 ppm per tube. One drop of a bacterial cellsuspension is then added to the appropriate tube. The bacterial cellsuspensions are taken from 24-hour broth cultures which have beeninoculated with bacteria from 7-day Nutrient Agar slants. Afterinoculation, the tubes are pennitted to stand at room temperature for 24hours, then placed in an incubation cabinet for an additional 24 hoursat 37 C., then examined and turbidity readings taken. The tubes arerated according to the following index:

0 no effect 9 kill of bacteria stasis. with no kill of all bacteria Theresults of these tests are reported in Table 1 below which shows themarkedly efiective antibacterial action of typical compounds of theinvention against the organisms vention is demonstrated by the followingtests wherein representative compounds are tested at a concentration of100 ppm of active ingredient against three organisms: Maniliniafructicola, the pathogen which incites American named. However, thecompounds of the invention exhibit also 5 brown rot of stone fruits;Sremphylium sarcinaeforme, the marked activity against a wide variety ofgram positive and pathogen responsible for leaf spot on certain legumes;and gram negative bacteria which are causal agents of disease inAspergillus niger, a saprophyte responsible for degradation of man andlower animals. Further, the compounds of the inventextiles, fabrics,leathers, vegetables and other organic materition are found to beefi'ective against protozoa, such as als. Trichomonas vaginalis. 10

In the test, spores from the separate cultures of the aboveidentifiedorganisms are washed with deionized water and filtered to remove piecesof mycelium. Two milliliters of orange TABLE I juice are added per literof spore suspension to facilitate germ Antibacterial activity 1suspension. For each fungus species in test, a small amount of sporesuspension plus a sufficient amount of stock solution of test compoundare added to individual opticlear vials. The Efffffgffifil amount ofstock solution employed is sufficient to provide ap- Structure of testCompound 100 100 100 proximately 100 ppm of active ingredient in themixture of spore suspension and stock solution. The vials are stoppered,N placed on a tumbler, and rotated for 24 hours to provide posi- 0 q 9tive contact of the test compound and the test organism. At OzN C=N--N'%the end of the 24-hour exposure period, the suspensions are s I examinedmacroscopically and the percent inhabitation of 25 spore germinationrecorded.

5 5 5 The results of these tests appear in Table ll below. on: l-CH=CHS/ If TABLE II 113 I Percent inhibition 01 Spore germination 9 9 q1%0111 hSZIem- Aim;- l |l inia p yxum m- OZN jrucsarcinaelus I NH tiralafarme nlazr Concentration (p.p.m.) N l O 9 9 9 Structure of testcompound 100 lOO 100 om --CH=NN- N 00 s I 40 l $1 100 100 0 N C=NN O H ON N-N N 95 D 10f! l M 0 9 g l J O N NH O N CH=NO II 7 s s 2 s N J I n q9 I N 100 0 100 OzN CH=H-OH LNG, S s

i Tu 9 5 9 /NO2 H NH S I 0 O cN-N N EXAMPLE 23 0 0 9 I I L 1 S Thenematocrdal activity of the compounds of the instant invention areexemplified by the following tests, wherein EXAMPLE 22 The fungicidalactivity of the compounds of the instant inrepresentative compounds aretested at a 1000 ppm concentration against the vinegar eelworm,Turbatrix aceti.

In these tests an aqueous suspension containing approximately nematodesis placed in a number of small jars and a sufiicient amount of testcompound added to each to provide a concentration of approximately 1000ppm of test compound in each mixture. The jars are placed on a tumblerand rotated for 24 hours, then examined macroscopically to determine thepercent mortality achieved. The results of these tests are providedbelow.

3,674,780 9 r 10 g TABLE III EXAMPLE 24 Percent kill of nematodes,

fii'g; The herbicidal activity of the compounds of the instantinconcentration 5 vention is shown by the following tests wherein a 1.5percent Difco-Bacto agar containing 500 ppm or 100 ppm of test com- 1100 pound is poured into small bottles and permitted to solidify. Aftersolidification, seeds of wheat, radish, cucumber and L corn areindividually placed on the surface of the solidified S CH=CH 10 agar. Asmall amount of water is added to each bottle and the bottles arecovered with glass plates for 48 hours to prevent or I 100 minimize theescape of volatile chemicals in the test. After 48 hours, the glassplates are removed and the bottles covered with Kraft paper. The seedsand plants are observed periodi- S N 15 cally following treatment andwater is added as required. At

69 6 the end of the 3-week test period, all bottles in test are examinedand rated according to the phytotoxicity index pro- T yi sq bani-h ,W WOzN SiCH=N-OH 2 l l The results of the tests are provided in Table IVbelow TABLE IV Phytotoxicity oi Wheat R'adish Cucumber CornConcentration (p.p.m.)

Structure of test compound 600 100 500 100 600 100 500 100 N I oiN-J/CH=CH TABLE IV Phytotoxlcity i Wheat Radish Cucumber CornConcentration (p.p.m.)

Structure of test compound 500 100 500 100 500 100 500 100 TN 9.. 9 r0.0,.

JN0z S cH=N-N Nori:.-Pl1ytotoxicity index: 0=Normnl, like chock; 9=Snnddead; X=Plant dead; 7=R0ots dead; 6= Blind germination; =Gorminutu, row,than die; 4=L -ad malformation; 3=Chlorosis; 2=Suppressed growth,1=Elongute stems.

We claim: 0 0

1. A 2,5-disubstituted thiazole of the formula: M ,\r e

I 0 NH and .\'n N i I y 0 Y X r n where X and Y each represents [asaturated S-membered-mononitrogen heterocyclic, a saturatedS-membercd-dinitrogen heterocyclic, a saturated 5-membered-mononitrogen-monooxygen heterocyclic, each of saidheterocyclics containing at least one but not more than two carbonylgroups in the heterocyclic moiety, wherein each of said heterocyclics isbound at the ring nitrogen;]and R stands for -H or COCH 2. The compoundaccording to claim 1: 3-{[(5-nitro-2-thiazolyl)methylidene]amino}-2-oxazolidinone.

3. The compound according to claim 1: 2-amino-5-( S-nitro- Z-thiazolyl)-l ,3,4-thiadiazole.

4. The compound according to claim 1: 1-{[(5-nitro-2-thiazolyl)methylidene1amino}-2imidazolidinone.

II i t i I TED STATES PATE @FFEQE Patent No. 3 7; 7 1 Dated July L, 1972Inventor(s) Gerald Berkelhammer, Goro Asato and Edward Leslie Moon It iscertified that error appears in the above-identified patent and thatsaid Letters Patent: are hereby corrected as shown below:

Column 12, lines 26-31, the following should be deleted:

[a saturated 5-membered-mononitrogen heterocyclic,

a saturated S-membered-dinitrogen heterocyclic, a saturated5-membered-mononitrogen-monooxygen heterocyclic, each of saidheterocyclics containing at least one but not more than two carbonylgroups in the heterocyclic-moiety, wherein each of said heterocyclics,is bound at the ring nitrogen;

Signed and sealed this 5th day of December 1972.

(SEAL) Attest:

EDWARD M.FLBJTCHER,JRQ ROBERT GOTTSCHALK Attesting Officer Commissionerof Patents FORM PC7-1050 (10-69) USCOMM-DC 60376-P69 R u .v aovnmannrlmmnc omcz ans c-asu-au

2. The compound according to claim 1:3-(((5-nitro-2-thiazolyl)methylidene)amino)-2-oxazolidinone.
 3. Thecompound according to claim 1:2-amino-5-(5-nitro-2-thiazolyl)-1,3,4-thiadiazole.
 4. The compoundaccording to claim 1:1-(((5-nitro-2-thiazolyl)methylidene)amino)-2imidazolidinone.